The CMRF58 antibody recognizes a subset of CD123hi dendritic cells in allergen-challenged mucosa

Abstract

CD123hi CD11c− dendritic cells (CD123hi DC) are a distinct subset of human DC present in bone marrow, blood, lymphoid organs, and peripheral tissues. Pathogen stimulation, cytokine, or CD40 ligation induces CD123hi DC maturation, involving a shift from their innate immune to cognate antigen-presenting functions. In this study, we revealed that blood CD123hi DC in the presence of cytokine (granulocyte macrophage-colony stimulating factor and interleukin-3) undergo progressive, step-wise maturation through an “early” stage, delineated by expression of the antigen detected by the new monoclonal antibody CMRF58 (CD123hiCMRF58+CD40−CD86−CD83−) to the “late” stage with costimulatory antigen expression (CD123hiCMRF58+CD40+CD86+CD83+/−). In this early stage, cytokine-maintained CD123hi DC do not display changes in their morphology, no longer produce interferon-α (IFN-α) in response to bacteria, and develop the capacity to induce proliferation and polarization of allogeneic T cells. CD123hiCMRF58+ DC, phenotypically similar to in vitro cytokine-maintained CD123hi DC, were not detected in tonsil but are present in allergen-challenged nasal mucosa of allergic individuals. Thus, CD123hi DC in certain tissue environments such as allergen-challenged nasal mucosa share a common CD123hiCMRF58+ phenotype with in vitro cytokine-maintained blood CD123hi DC characterized by lack of IFN-α production.